Employing sensitive hybridization and molecular cloning techniques that allow identification and isolation of nucleotide sequences exhibiting as little as 60-70% homology to the probes employed, we have identified novel families of distantly related endogenous retroviruses in a variety of vertebrate species from avian to primate, including man. In addition to the identification of novel ancient endogenous retroviruses, these procedures have revealed the presence of retrovirus-related genetic sequences that are present individually (solo) throughout the eukaryotic genome presumably as retrotranspons or severely deleted endogenous proviruses. Utilizing similar hybridization techniques, we have recently identified nucleotide sequences exhibiting homology to HIV-related genetic sequences in uninfected human DNA. Because of the presence of these HIV- related genetic sequences in uninfected human DNA and the potential ramifications of these sequences to the origins and pathogenicity of HIV, we propose to: 1) isolate and characterize these HIV-related genetic structures present in human DNA by molecular cloning and nucleotide sequencing, respectively, in an effort to delineate their precise nature; 2) determine whether these structures are present in other vertebrate genera in an attempt to determine their evolutionary relationships with related structures in disparate cell types, if present; and 3) begin to identify and characterize the transcriptional HIV-related genetic structures if indeed they can be detected. If these HIV-related genetic structures can be substantiated by nucleotide sequence analysis and can further be demonstrated to be expressed in human cell, then we would ultimately determine the biological consequences of the expression of these endogenous HIV-related genetic structures in vivo in an effort to determine whether they play a role in HIV-infection in patients exhibiting asymptomatic, symptomatic, or terminal consequences of disease. THe methodologies that we plan to employ to achieve these objectives are for the most part already implemented in our laboratory and include a variety of physicochemical, enzymological, and molecular biological techniques available for the analysis of DNA, RNA, and protein.